We propose to purchase a ZEISS Xradia 520 Versa 3D X-ray microscope (XRM). This is a state-of-the-art imaging system for non-destructive, submicron resolution, high-contrast, 3D X- ray computed tomography imaging of biological tissues. There is no comparable system at our institution (Washington University) nor in our state (Missouri). We have assembled a group of 19 Major and Minor Users at our institution whose research is currently limited by lack of an instrument with the features of the Xradia 520 Versa. Their research programs will benefit greatly from local access to this instrument. These users are supported by 44 current NIH research grants from six institutes (NCI, NHLBI, NIA, NIAMS, NICDH, NIGMS), totaling $9.6 million direct costs/year. The instrument will be located in the Washington University Musculoskeletal Research Center, and managed through the existing Musculoskeletal Structure and Strength Core (MSSC; MJ Silva, Director). The MSSC is a service and consultation core supported by an NIH P30 Core Center grant (AR057235). Addition of the proposed instrument will enhance the technical capabilities of the core and provide access to state-of-the-art XRM imaging to the biomedical research community at Washington University. The research projects of the Major and Minor Users are focused on basic and pre-clinical studies related to many health conditions, including osteoporosis, arthritis cancer, cardiovascular disease, scoliosis and fracture healing. A common need is for high-resolution, high-contrast, non-destructive imaging of model organisms (e.g., mouse, zebrafish), which the proposed instrument will deliver. Imaging applications of the instrument include: bone porosity; vascularity in fracture healing and metastatic tumors; articular cartilage and joint tissues; bone microdamage; adipose tissue; skeletal, cardiac and lung development. The instrument will allow the users to assess outcomes that currently we cannot assess (e.g., osteocyte lacunar number, articular cartilage thickness, microvascular vessel volume, adipocyte volume) and to do so with non-biased sampling of 3D volumes. In closing, the proposed instrument will enhance the biomedical research infrastructure at Washington University, provide access to state-of-the-art imaging not available on our campus, and accelerate the pace of health-related research projects. This is consistent with the long-term goals and mission of Washington University.